20-45547503-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000651288.1(EPPIN-WFDC6):c.-146C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,476,842 control chromosomes in the GnomAD database, including 50,974 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5372 hom., cov: 31)

Exomes 𝑓: 0.26 ( 45602 hom. )

Consequence

EPPIN-WFDC6
ENST00000651288.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.166

Publications

5 publications found

Variant links:

Genes affected

EPPIN-WFDC6 (HGNC:38825): (EPPIN-WFDC6 readthrough) This locus represents naturally occurring read-through transcription between the neighboring SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) and WFDC6 (WAP four-disulfide core domain 6) genes. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

EPPIN-WFDC6 links:

EPPIN (HGNC:15932): (epididymal peptidase inhibitor) This gene encodes an epididymal protease inhibitor, which contains both kunitz-type and WAP-type four-disulfide core (WFDC) protease inhibitor consensus sequences. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene is a member of the WFDC gene family and belongs to the telomeric cluster. The protein can inhibit human sperm motility and exhibits antimicrobial activity against E. coli, and polymorphisms in this gene are associated with male infertility. Read-through transcription also exists between this gene and the downstream WFDC6 (WAP four-disulfide core domain 6) gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

EPPIN links:

ENSG00000237464 (HGNC:):

ENSG00000237464 links:

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new If you want to explore the variant's impact on the transcript ENST00000651288.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651288.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPPIN	NM_020398.4	MANE Select	c.-146C>A	upstream_gene	N/A	NP_065131.1	O95925-1
EPPIN-WFDC6	NM_001198986.2		c.-146C>A	upstream_gene	N/A	NP_001185915.1
EPPIN	NM_001302861.2		c.-146C>A	upstream_gene	N/A	NP_001289790.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPPIN-WFDC6	ENST00000651288.1		c.-146C>A	5_prime_UTR	Exon 1 of 5	ENSP00000498632.1	A0A494C0M2
EPPIN	ENST00000409554.1	TSL:5	c.-146C>A	5_prime_UTR	Exon 1 of 4	ENSP00000387153.1	B7ZBA9
ENSG00000237464	ENST00000803561.1		n.519+7226G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39887

AN:

151780

Hom.:

5359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.259

AC:

342867

AN:

1324946

Hom.:

45602

Cov.:

AF XY:

0.257

AC XY:

166727

AN XY:

648164

show subpopulations

African (AFR)

AF:

0.260

AC:

7706

AN:

29660

American (AMR)

AF:

0.377

AC:

10724

AN:

28422

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

5970

AN:

20838

East Asian (EAS)

AF:

0.435

AC:

15405

AN:

35390

South Asian (SAS)

AF:

0.229

AC:

15421

AN:

67326

European-Finnish (FIN)

AF:

0.268

AC:

8715

AN:

32468

Middle Eastern (MID)

AF:

0.240

AC:

901

AN:

3748

European-Non Finnish (NFE)

AF:

0.251

AC:

263750

AN:

1051878

Other (OTH)

AF:

0.259

AC:

14275

AN:

55216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13118

26236

39354

52472

65590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9418

18836

28254

37672

47090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.263

AC:

39929

AN:

151896

Hom.:

5372

Cov.:

AF XY:

0.261

AC XY:

19402

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.260

AC:

10790

AN:

41466

American (AMR)

AF:

0.287

AC:

4374

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

991

AN:

3466

East Asian (EAS)

AF:

0.412

AC:

2107

AN:

5112

South Asian (SAS)

AF:

0.230

AC:

1108

AN:

4814

European-Finnish (FIN)

AF:

0.265

AC:

2799

AN:

10560

Middle Eastern (MID)

AF:

0.229

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.248

AC:

16811

AN:

67912

Other (OTH)

AF:

0.276

AC:

581

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1493

2986

4479

5972

7465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.225

Hom.:

1335

Bravo

AF:

0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.53

PhyloP100

0.17

PromoterAI

0.034

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over